Adams has recently demonstrated that ultra-long peripheral nerve blocks can be achieved in vivo by using combinations of lidocaine and saxitoxin (or tetrodotoxin.) These two drugs are highly synergistic both from the standpoint of axonal blocking potency and blocking duration. The active component of STX and TTX is thought to be the guanidinium moiety and other guanidinium compounds have been shown to have local anesthetic activity though much less potent than STX or TTX. The purpose of these investigations is to find out if combinations of local anesthetics and guanidinium compounds other than TTX and STX are synergistic; if such combinations can be used to give long duration blocks; if they have a better therapeutic to toxic ratio than standard local anesthetics; if STX or TTX can be safely used for nerve block; and finally, how these drugs work separately and together. The questions will be answered with a series of experiments going from the single axon to the whole animal. Mechanisms of action and synergism will be investigated in the frog single fiber and nerve trunk (sciatic). Rats and cats will be used for the in vivo studies. Infiltration of rat sciatic nerves will uncover the potential for tissue toxicity and at the same time give an idea of how long a block can be expected to last. Finally, cats will receive the drugs intravenously in order to determine the effects of these compounds on the neuromuscular, cardiovascular, and central nervous systems.